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Gene expression profiling demonstrates that TGF-{beta}1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-{beta} signaling.

Author:
  • Göran Karlsson
  • Yingchun Liu
  • Jonas Larsson
  • Marie-Jose Goumans
  • Ju-Seog Lee
  • Snorri S Thorgeirsson
  • Markus Ringnér
  • Stefan Karlsson
Publishing year: 2005
Language: English
Pages: 396-403
Publication/Series: Physiological Genomics
Volume: 21
Issue: 3
Document type: Journal article
Publisher: American Physiological Society

Abstract english

Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-β-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.

Keywords

  • Hematology
  • Cancer and Oncology
  • signal transduction
  • Smad
  • microarrays

Other

Published
  • ISSN: 1094-8341
Markus Ringnér
E-mail: markus [dot] ringner [at] biol [dot] lu [dot] se

Research engineer

Molecular Cell Biology

B-A314c

Sölvegatan 35, Lund

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